Steroid Receptors Reprogram FoxA1 Occupancy through Dynamic Chromatin Transitions
Open accessAbstract
The estrogen receptor (ER), glucocorticoid receptor (GR), and forkhead box protein 1 (FoxA1) are significant factors in breast cancer progression. FoxA1 has been implicated in establishing ER-binding patterns though its unique ability to serve as a pioneer factor. However, the molecular interplay between ER, GR, and FoxA1 requires further investigation. Here we show that ER and GR both have the ability to alter the genomic distribution of the FoxA1 pioneer factor. Single-molecule tracking experiments in live cells reveal a highly dynamic interaction of FoxA1 with chromatin in vivo. Furthermore, the FoxA1 factor is not associated with detectable footprints at its binding sites throughout the genome. These findings support a model wherein interactions between transcription factors and pioneer factors are highly dynamic. Moreover, at a subset of genomic sites, the role of pioneer can be reversed, with the steroid receptors serving to enhance binding of FoxA1.
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Chromatin loading of FoxA1 (a well-established pioneer factor) was shown to need assistance by non-pioneer TFs in a signal-dependent manner.
“For example, the chromatin loading of FoxA1 (a well-established pioneer factor), was shown to need assistance by non-pioneer TFs in a signal-dependent manner35.”
From Synergistic gene expression during the acute phase response is characterized by transcription factor assisted loading (2017) · cites this paper as [35]
Assisted loading has been described in various systems.
“Assisted loading has been described in various systems30–37.”
From Synergistic gene expression during the acute phase response is characterized by transcription factor assisted loading (2017) · cites this paper as [35]
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References 48 · Cited by 312
Research works printed but not linked: 39
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- Authors
- Swinstead, E. E., Miranda, T. B., Paakinaho, V., Baek, S., Goldstein, I., Hawkins, M., Karpova, T. S., Ball, D., Mazza, D., Lavis, L. D., Grimm, J. B., Morisaki, T., Grøntved, L., Presman, D. M., & Hager, G. L.
- Affiliations
- National Institutes of Health (US)
- Vita-Salute San Raffaele University (IT)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Hager, Gordon L.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2016-04
- Volume
- 165
- Issue
- 3
- Pages
- 593-605
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC4842147
- OpenAlex
- W2314176140
- Cited by
- 312
- References
- 48
- Citations by year
- 2026: 16 · 2025: 24 · 2024: 30 · 2023: 25 · 2022: 33 · 2021: 43 · 2020: 27 · 2019: 34 · 2018: 32 · 2017: 30 · 2016: 18
- FWCI
- 30.70
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
- CONICET Digital (CONICET) (submittedVersion, cc-by-nc-sa)
- Funders
- Villum Fonden (00007292)
- Lundbeckfonden (R194-2015-1060)
- Novo Nordisk Fonden (NNF14OC0013333)
- National Institutes of Health
- National Cancer Institute (Z01BC005450)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- FOXA1, estrogen receptor, glucocorticoid receptor, pioneer factors, chromatin occupancy, transcription factor interaction, chromatin dynamics, single-molecule tracking, breast cancer, steroid hormone receptors, chromatin accessibility
- MeSH terms
- Chromatin, Deoxyribonucleases, Humans, Receptors, Estrogen, Receptors, Glucocorticoid, Transcription Factors, Hepatocyte Nuclear Factor 3-alpha, MCF-7 Cells
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